Advances of pharmaceutical science revealed that biological system has the ability of distinguishing individual members of a pair of enantiomeric compounds, and thus giving different responses. In other words, the receptor sites in biological systems have three-dimensional surface structure that consists of distinct grooves and cavities. These receptors interact only with three-dimensional molecules with complementary structures. Therefore, depending on the steric conformation of the molecule that links to the receptor, the biological results may vary significantly. One enantiomer may demonstrate highly potent therapeutic power towards certain disease while the other enantiomer is either inactive or highly toxic. For example, Thalidomide, a widely used sedative by many pregnant women in the 1960s, was identified as teratogenic. It was found that the feto-toxic activity was only associated with one of the enantiomers, the S-form. The other enantiomer, the R-Thalidomide, could be a safe drug theoretically. On the other hand, processes that produce only the desired enantiomers are more cost effective than those that produce racemic mixtures since the costs related to separation of the two enantiomers from the racemic mixture are avoided. To prevent a repetition of tragedy like Thalidomide, reduce production cost, and meet increasingly restrict FDA guidlines, tremendous effort has been directed towards developing highly efficient and reliable process for production of desired molecule in enantiomerically pure state. It has been estimated that more than 50% of the top-selling drugs are enantiomerically pure, and up to 80% of drugs currently under development are chiral. Of all available methods, chiral catalyst mediated asymmetric synthesis is one of the most efficient, versatile, cost effective, and environment friendly processes to obtain enantiomerically pure compounds, which has been evidenced by the explosive growth of research reports in this area and recent awarding of 2001 Nobel prize in chemistry to William S. Knowles, Ryoji Noyori and K. Barry Sharpless for their pioneering research work in asymmetric synthesis using chiral catalyst. In addition to its widespread applications in basic research and pharmaceutical industry, asymmetric catalysis is also used extensively in other industries such as agrochemical, animal health, flavor and fragrance, liquid crystal material, and polymer, etc.
Generally, the chiral catalysts used in many asymmetric reactions consist of transition metals and chiral ligands. In most cases, the asymmetric transformations were accomplished via a preferred asymmetric transition state derived mainly under the influence of the chiral ligand. The unique chiral structure of ligand was essential for the activity, enantioselectivity, and lifetime of a given catalyst. Chiral phosphine ligands have been an integral part of many successful chiral catalysts used in asymmetrical catalysis. However, factors vital to catalyst activity, stereoselectivity, and lifetime are often reaction specific and not well understood. Tremendous effort has been directed towards is design and synthesis of chiral phosphine ligands to maximize activity, stereoselectivity, and lifetime of chiral catalysts. A comprehensive review article on phosphine ligand was recently published (Laurenti, D. and Santelli, M. Org. Prep. Proc. 1999, 31(3), 245-294.).